N-acyl-3,4-dihydro-oxazine-(1,3) compounds for controlling phytopathogenic fungi

ABSTRACT

N-acyl-3,4-dihydro-oxazine-(1,3)-derivatives of the formula IN WHICH A represents a sulphur or an oxygen atom, R1 indicates a six-membered ring condensed with the dihydro-oxazine ring and R2 represents an aliphatic or aromatic residue are very effective compounds for controlling plantpathogenic fungi.

United States Patent Huber-Emden [is] 3,678,046 51 July 18,1972

[54] N-ACYL-3,4-DIHYDRO-OXAZINE-(l,3)

COMPOUNDS FOR CONTROLLING PHYTOPATHOGENIC FUNGI [72] lnventor: Helmut Huber-Emden, Basel, Switzerland [731 Assignee: Ciba Limited, Basel, Switzerland [22] Filed: April 27, 1970 211 App]. No.: 32,415

[30] Foreign Application Priority Data April 29, 1969 Switzerland ..6559/69 M slYiiq fl r 213311 5 17 [52] U.S. Cl. ..260/244 R, 260/152, 260/247. 1

260/247.2 A, 260/247.5 B, 260/287 R, 260/288 R, 260/454, 260/465 D, 260/558 R, 260/558 D, 260/562 R, 260/562 S, 260/562 8, 424/226,

OTHER PUBLICATIONS McDonagh et al. J. Org. Chem. Vol. 33, a es 1- 8 1968 QD241J6 p g Primary Examiner- Natalie Trousof Anomey-Harry Goldsmith, Joseph A. Kolodny and Mario A. Monaco ABSTRACT N-acyl-3,4-dihydro-oxazine-( l ,3 )-derivatives of the formula a A N-- B2 R1 in which A represents a sulphur or an oxygen atom, R indicates a six-membered ring condensed with the dihydro-oxazine ring and R represents an aliphatic or aromatic residue tare ery effective compounds for controlling plantpathogenic ungi.

0 U, N-PI-R:

3 Claims, No Drawings N-ACYL-3,4-DlHYDRO-OXAZlNE-( l ,3) COMPOUNDS FOR CONTROLLING PHYTOPATHOGENIC FUNGI N--i JRa 7 R: i H t 9...... a. $9.

group by a carbon atom.

R is especially a fused-on substituted benzene residue, though heterocyclic ring systems are also suitable, for example, quinoline derivatives of the formula in which R has the meaning defined above, X represents a halogen atom, for example, a chlorine, bromine or iodine atom and R represents a hydrogen atom or a methyl group.

Preferred N-acyl-3,4-dihydro-oxazines of the formula (I) are compounds of the formula I 0 v Nii-Rr Us M. M .11!.

in which at least one of the U-substituents, preferably U represents a halogen atom, a possibly halogen-substituted alkyl group containing one to four carbon atoms, a hydroxyl or nitro group or an alkoxy or alkenyloxy group containing up to four carbon atoms or a possibly halogen-substituted phenyl group which is bound to the fused-on benzene residue either directly or through an azo group and the other U-substituents each represents a hydrogen atom or one of the afore-mentioned substituents, and R represents an aliphatic or aromatic residue bound to the carbonyl group through a carbon atom.

The term aliphatic residue" as used above and hereinafter describes an alkyl, halogenoalkyl, cyanoalkyl, thiocyanoalkyl, alkenyl or halogenoalkenyl group containing one to five carbon atoms, an ethylmercaptomethyl or morpholinomethyl group, while an aromatic residue is a phenyl group which may be unsubstituted or preferably substituted by halogen or nitro.' The present invention also provides a method of controlling phytopathogenic fungi which comprises applying to a crop area a compound of the general formula (I) or a preparation comprising as active ingredient a compound of the general formula (I), together with a carrier and/or other additive.

The invention also provides the compounds of the formula r or... V)

in which U represents an alkoxy or alkenyloxy group containing one to four carbon atoms, the substituents U,', U, and U represent hydrogen atoms or at most two of them represent a halogen atom, an alkyl group containing one to four carbon atoms (preferably methyl or ethyl) and/or a nitro group, and R represents an aliphatic or aromatic residue as defined above which is bound to the carbonyl group through a carbon atom and pesticidal preparations that contain a compound of the formula (IV) as active ingredient in conjunction with one or more further additives.

According to an advantageous method of manufacturing the N-acyl-3,4-dihydro-oxazine-(1,3) derivatives of the formula (l), a compound of the formula in which R, and R, have the meanings defined above, is reacted in an anhydrous medium that contains an inert organic' solvent or concentrated sulphuric acid, with formaldehyde or a formaldehyde donor in the presence of an acidic catalyst and, if desired, performing further reactions in the acyl residue.

Preferred starting materials methylphenols of the formula C Hz-NH-C 0-182 are ortho-acylaminois reacted with an anhydrous inert organic solvent or in concentrated sulphuric acid as reaction medium with formaldehyde or a formaldehyde donor in the presence of an acid catalyst and, when R, contains an alkenyl group, if desired halogen is added on or, if desired, hydrogen halide is eliminated.

The N-acyl-3,4-dihydro-oxazine-( 1,3) derivatives of the formula (1) or (IV) obtained by the methods described above may be used. for example. in the following reactions without affecting the oxuzine system:

a. By means of phosphorus pentasulphide the acyl group can be converted into the corresponding thioacyl group, according to Pa s l 2 N- R:

b. As is mentioned above, C1 or Br can be added on to R, when R contains an alkenyl bond, and from the resulting N- di-haloalkyl-dihydro-oxazine-( 1,3) derivatives HCl or l-lBr can be eliminated in the usual manner with formation of a chloroor bromo-alkenyl group.

The N-acyl-3,4-dihydro-benzoxazines-(1,3) of the formula (III) or IV) can be manufactured in the known manner from a corresponding phenol with at least one free ortho-position according to the two-stage process:

In the first stage the phenol is reacted with an N-methylol- This reaction is carried out in a solvent, preferably in alcohol or glacial acetic acid, in the presence of a strongly acidic catalyst, for example, concentrated hydrochloric acid, HCl gas, phosphoric acid or pyrophosphoric acid. In some cases it is possible to work directly in concentrated sulphuric acid as reaction medium, and in such a case the acidic catalyst can be dispensed with.

In the second stage the resulting condensation product (B) is reacted with paraformaldehyde (or a formaldehyde donor) to the desired benzoxazine:

N-ii-R:

(III) This reaction is carried out in a solvent, for example, benzene, toluene, xylene, chlorobenzene or a mixture of benzene and dioxan, in the presence of an acidic catalyst, for example, para-toluenesulphonic acid (cf. French Pat. No. 1,555,544).

In some cases it is possible here too to work directly in concentrated sulphuric acid as reaction medium and as catalyst, but this furnishes the desired benzoxazines of the formula (III) only when U and U do not represent hydrogen.

When both reaction stages (1) and (2) are carried out in concentrated sulphuric acid as reaction medium, the isolation of the intermediate product (B) can be dispensed with, and the two stages are performed successively in the same starting mixture as illustrated by the two examples of manufacture described below.

The active substances of the formula (I) display a very good activity against representatives of the class Phycomycetes, for example, phytopathogenic fungi, for example, Botrytis and Piricularia, and also against various other pathogenic fungi affecting grain crops, soyabean, corn, rice, vegetables, fruit and other cultures.

They act especially against the following kinds of fungi:

Cochliobolus miyabeanus species, Corticium species, Cerospora species, Alternaria species, Venturia inacqualis, Podosphaera leucorricha, Uramyces phaseoli, Cercospora apii, Cencospora beticala, Cervospora musae, Piricularia sp., Erysiphe cichoracearum, Penicillium digitatum, Sphaeroteca humuli, Diplocarpon rosae, Uncinula necalor, Coccomyces hiemalis, Cladosporium carpophilum, Erysiphe graminis harder, Monolinia (Sclerotinia) Laxa, Monolim'a (Sclerotinia) frucu'cola, Piricularia oryzae, Puccinia recondita, P. caronala, P. glumarum, Puccinia gramim's tritici, Aspergillus niger, Aspergil- Ius terreus, Rhizocronia, F usarium, Verticillium. This list does not claim to be complete.

The present invention also provides preparations which comprise as active ingredient a compound of the general formula (I), together with a carrier.

The active substances of this invention, as well as preparations containing them, also display a toxic activity towards fungi that attack plants in the soil and partially cause tracheomycoses, for example, Fusarium cubense, Fusarium dianthi, Verticillium alboatrum and Phialophora cinerecens.

It was unexpected that the compounds of the formula (I) combine a pronounced phytomicrobicidal activity with an excellent plant compatibility. Even when applied in substantial quantities, as may happen accidentally, no damage to the plants occurs.

The active substances of the formula (I) can be used as such to control harmful fungi; for this purpose devices are used that produce extremely fine sprays or dusts to prevent overdosages as far as possible. It is of advantage to apply the products by spraying from aircraft, for which purpose suitable fungicidal preparations may be used instead of the pure substances.

The active substances may be formulated as liquid or solid, dry or moist products, containing 0.1 to percent by weight of active substance, being in the form of solutions, emulsions, suspensions, concentrates, wettable powders, dusting agents or granulates.

The amount to be applied varies as. a rule from 0.01 to 5 kg of active substance per hectare.

The sprays for direct use contain, for example, mineral oil fractions having a high to medium-high boiling range, especially above C, for example, Diesel oil or kerosene, or coal tar oil or oils of a vegetable or animal origin, also hydrocarbons, for example, alkylated naphthalenes, tetrahydronaphthalene, xylene mixtures, cyclohexanols or if desired furthermore ketones, chlorinated hydrocarbons, for example, tetrachloroethane, trichloroethylene or triand tetrachlorobenzenes.

For use in the form of aqueous preparations there are used emulsion concentrates, pastes or wettable powders with addition of water. Suitable emulsifiers or dispersants are non-ionic products, for example, condensation products of aliphatic alcohols, amines or carboxylic acids with a long-chain hydrocarbon residue of about 10 to 30 carbon atoms with ethylene oxide, for example, the condensation product of octadecyl alcohol with 25 to 30 mols of ethylene oxide, or of soyabean fatty acid with 30 mols of ethylene oxide, or of commercial oleylamine with 15 mols of ethylene oxide, or of dodecylmercaptan with 12 mols of ethylene oxide. It is also possible to use condensation products of ethylene oxide with hydro-aromatic polycyclic carboxylic acids or amines. From among suitable anionic emulsifiers there may be mentioned: the sodium salt of dodecyl alcohol sulphuric acid ester, the sodium salt of dodecylbenzenesulphonic acid, the potassium or triethanolamine salt of oleic or abietic acid or of mixtures of these two acids, or the sodium salt of a petroleumsulphonic acid. Suitable cationic dispersants are quaternary ammonium and phosphonium compounds, for example, cetyl pyridinium chloride or dioxyethylbenzyl-dodecyl ammonium chloride.

When the new preparations are to be used in the form of dusting or casting agents, they may contain as solid vehicles talcum, kaolin, bentonite, sand, calcium carbonate, calcium phosphate, or coal, cork meal or wood meal or other materials of vegetable origin. The various preparations may contain the usual additives that improve the distribution, adhesion or penetration; such substances are, for example, fatty acids, resins, glue, casein or, for example, alginates. It is also very advantageous to use the preparations in granulated form. The pesticidal preparations may contain the new compounds as the only active substance or in form of a combination with other insecticides, acaricides, nematocides, fungicides, herbicides or fertilizers, for example also trace elements.

It is specially advantageous to use granulated formulations, primarily for use in water rice cultures.

To prepare a granulate the active substance is dissolved in an organic solvent, this solution is absorbed on a granulated mineral, for example, attapulgite, granicalcium, pumice stone or silica, and the solvent is then expelled.

Alternatively, the granulates can also be manufactured by mixing the active substance of the formula (I) with a polymerizable compound and polymerizing this mixture in such manner that the active substance is left unaffected and at the stage of the gel formation granulation is carried out.

Granulates based on polymers and distinguished by a more differentiated release of the active substance are obtained when the carrier granulate has a favorable adsorption: desorption ratio on the surfaces of the porous material so that it can be impregnated with corresponding active substances. A prerequisite for this method is that there is good adhesion between active substance and support and the release of the active substance in situ is calibrated. Preferred polymer granulates are formaldehyde resins with urea, dicyandiamide, or melamine, polyesters and polyacrylonitrile.

As mentioned above, the active substances of the formulas (I) to (1V) may be mixed with other commercial pesticides; in many cases this broadens the activity spectrum, in many other cases a synergistic effect is thus achieved.

As examples of fungicidal compounds which can be mixed with the active substances of the formulas (l) to (1V) there may be mentioned: Nabam, zineb, maneb, amobam, ziram, ferbam, thiram, urbazide, tetmosol, thioneb, glyodine, captan, oxine, cyclohexamide, DHA, omadin, dyrene, gliotoxin, vanicide, diamthazole, rhodamine, griseofulvin, karathan, dichlor, chloranil, techmazene, quintozene, botram, nirite, cerenox, dithionanone, dexone, bulbosan, caprocol, kresatin, dichlorophene, orthoxenol, shirlan, penchloral, preventol, hexachlorophene, dodin, zephiran, tin compounds, for example, phenetine acetate or hydroxide, urbasulph, sorbic acid, cetab, captan, dieldrin mesulfan, micofur, catechol, isothan, biopal, octone, irgasan-CF dinoterbon, dino penton, dinocton, chinothionate and chinomethionate.

The above list contains only some types of fungicidal compounds shown here for explanation.

The following Examples illustrate the invention.

EXAMPLE 1 Manufacture of:

C1 n-oo-omol 32.6 Grams of 2,4-dichlorophenol were dissolved at 40C in 65 ml of concentrated sulphuric acid. The solution was then cooled to 30to 35C and while cooling at this temperature 26.1 g of powdered N-methylolch1oro-acetamide werestirred in within 20 minutes. The whole was stirred until allhad dissolved and then kept in a closed vessel for 3'hours at room temperature.

Then 6.3 g of paruformuldehydc were stirred in during 20 minutes, stirring was continued for l hour (during which a slightly exothermic reaction was observed) and then the whole was kept in a closed vessel overnight.

The reaction solution was then poured into a mixture of 200 ml of chloroform, 200 ml of water and 60 g of ice, the organic phase separated, extracted with 100 ml of ZN-sodium hydroxide solution, washed neutral with water, treated with sodium sulphate and a small quantity of active carbon and the solvent was distilled off, at the end under vacuum.

As a crystalline residue there were obtained 40 g 71 percent of the theoretical yield) of compound No. 2 in an almost analytically pure form. Melting point: 1 1 1 to 1 12C.

EXAMPLE 2 A. Manufacture of:

2-(ehloroacetylamidomethyl)-4-ethoxyphenol 69.1 Grams of hydroquinone monoethyl ether and 37.0 g of N-methylolchloroacetamide were dissolved with heating in 250 ml of absolute ethanol. The solution was then cooled to 30C, 20 ml of concentrated hydrochloric acid were added while cooling externally and the whole was kept for 2 days in a closed vessel.

The solvent was then expelled under vacuum, the residual thick oil dissolved in 300 ml of chloroform, the undissolved matter (Nl-LCl) filtered off and the filtrate was neutralized by stirring it with NaHCO then washed with water, treated with sodium sulphate and animal charcoal and the solvent was expelled in a rotary evaporator. The residual viscous oil was dissolved in 200 ml of CCL, seeded, and then stirred overnight at 0C. 25 Grams of final product (melting at 100 to 108C) precipitated. After recrystallization from benzene or a larger quantity of carbon tetrachloride the melting point rises to 1 14 to 1 15C.

B. Manufacture of 2-l-l-3-(a-chloroacety1)-6ethoxy-3,4- dihydro- 1 ,3-benzoxazine CHrCl [Compound No. 53]

A solution of 20 g of the compound obtained in (A) in 300 ml of dry xylene, prepared at 110C, was cooled to C and 0.3 g of para-toluenesulphonic acid was added. While stirring vigorously, 2.7 g of paraformaldehyde were added during 1 hour at 80C, then a further 0.3 g of para-toluenesulphonic acid was added and the whole stirred for one-half hour at 80C; then 50 ml of the solvent was distilled 011, with 1 ml of water separating out in the distillate 68 percent of theory). The whole was cooled, thoroughly stirred with ml of 2N- sodium hydroxide solution and the organic phase was washed neutral, dried with sodium sulphate and the solvent distilled off under a water jet vacuum. A solid residue of 10.7 51 percent of the theoretical yield) of final product was obtained. Melting point: 108 to 1 10C.

The substance could be recrystallized from methanol and in the analytically pure form melted at 1 15 to l 16C.

In this or an analogous manner the following compounds of the formula 0 UP N--i :--n, J

were manufactured:

as well as the compound of the formula the formula (I) were dissolved in 2 liters of trichloroethylenei and sprayed in a fluidized bed granulator under a sprayingi [Cmp. No. 64] S pressure of 1.5 atmospheres over 9,230 g of porous urea/for- I I maldehyde granulate. When fluidizing air was heated to about 50C the solvent could be expelled. i c. To manufacture a granulate loaded with 7.5 percent of 0 active substance 770 g of a solid, commercial active substance 01 of the formula (I), 500 g of barium sulphate, 1,000 g of urea and 7,730 g of powdered, porous polyacrylonitrile were' In an analogous manner the following compounds of the log pressed n a roller mill and then disintegrated to the desired formula (II) were obtained: H H N MW Aw mm igrain size.

X A E EXAMPLE 4 I I Rice plants were grown in a greenhouse and then given a t isingle prophylactic spray with an aqueous spray broth contain- 9 Ting 0.1 percent each of active substance No. 2 or No. 17. Two I days later the 50 treated plants were infected with an aqueous conidial suspension of Piricularia oryzae Bri. et Cav. and incu- I ibated in a moist chamber. Seven days later the plants treated 5 with the preparations under test displayed a fungal infestation of 5 percent, whereas an infestation of up to 100 percent was 0mm X My" 0 C. jfoundon the untreated control plants.

H -H CH Cl Oil. EXAMPLE 5 -01 -H -CH:CH2 216-217. 5 t i I W 1%} I? 285 59 Bean plants were grown in a greenhouse and then given a -Br CH3 C 2 1 O lsingle prophylactic spray with an aqueous spray broth contain- 1 a we ing 0.1 percent of an active substanceof the formula (1). Two EXAMPLE 3 days later the plants thus treated were infected with uredo spores of Uromyces phaseoli (Pers.) Wint. and kept for 2 days Formulations of the Active Substances in a moist chamber. Afler a following incubation of 10 to 14 days in the greenhouse the following active substances agent revealed a complete or almost complete destruction of the Equal parts of an active substance according to this lnvenfunsuhz tion and of precipitated silicic acid were finely ground together. When this powder was mixed with'kaolin or talcum, Compound Lethal effect in dusting agents having a preferred content of l to 6 percent of active substance'could be prepared. 7 4 100 Spray powder i; r To manufacture a water-soluble spray powder the following 40 I8 loo ingredients were mixed and finely ground together: 20 100 50 parts of an active substance according to the invention 21 100 20 parts ofl-llSlL (highly adsorptivesilicic acid) I if; 82 25 parts of bolus alba (kaolin) 37 100 1.5 parts of sodium l-benzyl-2-stearyl-benzi-midazole-6,3'- 3 95 disulphonate 47 52 r 100 3.5 parts of reaction product of para-tertiary octylphenol 53 g with ethylene oxide. 62 v 60 Emulsion concentrate v 63 a. 40 Parts of an active substance of the formula (1) were mixed with 10 parts'of a mixture of an anionic surface-active 1 mp n (p y h i m o gn i m l of in an analogous test to establish the control effect against monolaurylbenzene-monosulphonic acid) andanon-ionic sur- Erysiph: cichoriacearum and Borrytis cinerea the compound face-active omp (P eferably a olye y n g y ether No. 53 revealed in both cases a lethal elreot of 95 percent. of monosorbitollaureate) and the whole was dissolved in a l l im;

small quantity of xylene, made up to 100 cc with xylene to 1, A m ound of the formula: form a clear solution which can be used as a spray concentrate e W and when poured into water as a stable emulsion.

b. Readily soluble active substances can also be formulated U as emulsion concentrates by mixing: 0

20 parts of active substance Us p; 70 parts of xylene 10 parts of a mixture of calcium dodecylbenzenesulphonate and a reaction product of an alkylphenol with ethylene 0 oxide. t n V t When this mixture is diluted with water to the desired concentration, a sprayable emulsion results. Y Granulate Y in which a. A solution of 7.5 g of one of the active substances of the 6, p esents alkoxy of from one to four carbon atoms or; formula (I) in 100 cc of acetone was poured over 92 g of. v alkenyloxy of from two to four carbon atoms, 1 granulated attapulgite (sieve: 24-28 mesh per inch). The each of s, and s, represents hy r gen, alkyl of from one whole was thoroughly mixed and the solvent expelled in a roto four carbon atoms or halogen, and tary evaporator to leave a granulate containing 7.5 percent of 2 r pres n s halogeno alkyl of from one to five carbon active Substance atoms, alkenyl or halogeno alkenyl of from two to five b. To manufacture a polymer granulate of 10 percentf carbon atoms, or phenyl optionally monosubstituted by S PEFM 1 .15 999 x 951?! .ast substance. of hmhilz 'i'lqfli iqaccording to claim 2. 

2. A compound according to claim 1 in which U6, represents alkoxy of from one to three carbon atoms, or allyloxy, each of U5, and U8, represents hydrogen, methyl or chlorine, and R2 represents chloromethyl, vinyl, monohalogenated vinyl, or chlorophenyl.
 3. The compound of the formula according to claim
 2. 